A method for the conversion of two different alcohols, R1OH, R2OH, into the unsymmetrical phosphodiester, (R1O)(R2O)P(O)OH without the isolation any intermediate, has been developed. Three methods for the conversion of the two alcohols to the triester dialkyl(1-methylacetonyl) phosphate without isolation intermediates have been discovered; the triester is purified and hydrolyzed to the diesters. The application of these methods to the synthesis of oligodeoxyribonucleotides and of oligoribonucleotides will be continued. BIBLIOGRAPHIC REFERENCES: F. Ramirez, J.F. Marecek and H. Okazaki, J. Amer. Chem. Soc., 97,7181 (1975). One-Flask Synthesis of Unsymmetrical Phosphodiesters. Selective Amine Catalysis of Phosphorylations of Primary vs Secondary Alcohols. F. Ramirez, H. Okazaki and J.F. Marecek, Synthesis, 637(1975). Acetoin Enediol Cyclophosphorochloridate.